Self-clearing catheters and methods of use thereof

ABSTRACT

Methods and catheters suitable for removing or reducing the formation of cellular occlusion associated the catheters. The catheters include a surface coated or infused with magnetic nanoparticles. Once the catheter is implanted in a subject, the nanoparticles induce localized hyperthermia around the catheter in response to a magnetic field.

CROSS-REFERENCE TO RELATED APPLICATIONS

This patent application claims priority to U.S. provisional patentapplication Ser. No. 62/121,920, filed on Feb. 27, 2015.

TECHNICAL FIELD

The present novel technology generally relates to medical devices, and,more particularly, to a catheter for reducing the likelihood of theformation of cellular occlusion at the site of central venous access.

BACKGROUND

Central venous catheters, also known as central venous access devices,have become a mainstay for patients requiring intravenous administrationof medications and other therapies. Unlike peripheral intravenouscatheters typically inserted into the veins of the hand or forearm,central access devices are inserted into large veins in the centralvenous circulatory system, for example into a large vein in the neck,chest, or groin. At present, central venous access devices have arelatively high failure rate, due in part to cellular obstructions orthrombus formation that can be lethal for patients.

For conditions such as hydrocephalus, one method to resolve these issuesis in situ recanalization after revision surgery and in-patientneurosurgery. Alternately, for central venous access, full replacementof these implanted devices is often required. Often, patients need to beconcomitantly treated with blood thinners, antibiotics and/or additionalmedications that may not otherwise be necessary and may likewise presentother unwelcome side effects. Therefore, both of these processes comewith additional cost, risk, and pain.

Accordingly, there is an ongoing need for improved catheters and likeimplantable devices that reduce the likelihood of formation of cellularocclusion at the site of central venous access devices in patients. Thepresent novel technology addresses this need.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 graphically illustrates the relationship between heating time andtemperature of a magnetically infused cannula according to a firstembodiment the present novel technology for various power input levels.

FIG. 2A is a schematic illustration of a cannula with a surface infusionof superparamagnetic nanoparticles according to the embodiment of FIG.1.

FIG. 2B is a schematic illustration of a cannula with a surface coatingcontaining a dispersion of superparamagnetic nanoparticles according tothe embodiment of FIG. 1.

FIG. 3A is a schematic drawing of a cannula of FIG. 2 as connected to afluid source.

FIG. 3B is a schematic drawing of a cannula of FIG. 2 having a coatingof uneven thickness and particulate concentration.

FIG. 3C is a schematic drawing of a cannula of FIG. 2 having an internalcoating.

FIG. 4 is a process flow diagram of a method for clearing occlusionsfrom an implantable device.

FIG. 5 is a process flow diagram of a method of preparing, inserting andin-situ cleaning an implantable device.

DETAILED DESCRIPTION

For the purposes of promoting an understanding of the principles of thenovel technology, reference will now be made to the embodimentsillustrated in the drawings and specific language will be used todescribe the same. It will nevertheless be understood that no limitationof the scope of the novel technology is thereby intended, suchalterations and further modifications in the illustrated device, andsuch further applications of the principles of the novel technology asillustrated therein being contemplated as would normally occur to oneskilled in the art to which the novel technology relates.

The present novel technology relates to methods and devices by which thelikelihood of formation of cellular occlusion at the site of centralvenous access devices in patients may be reduced.

Magnetic nanoparticle induced hyperthermia has been utilized in thetreatment of cancer cells. Chronically implantable devices, such asventricular catheters and central venous access devices, tend to havehigh failure rates due to mechanical cellular occlusion of the lumenand/or inlet pores. According to aspects of the present noveltechnology, chronically implantable catheters and like devices arecoated or surface-infused with superparamagnetic nanoparticles. Onceimplanted in a subject, the nanoparticles may be energized to inducelocalized hyperthermia in and around the implanted devices to reduceand/or remove cellular obstructions, and thus prolong device lifetime.The superparamagnetic nanoparticles are typically magnetite (Fe₃O₄),maghemite (γ-Fe₂O₃), or the like and are typically provided from 10 to100 nanometers in diameter, although the nanoparticles may be smallerthan 10 nm or larger than 100 nm as desired.

The temperature of the superparamagnetic nanoparticles may be increasedby applying an alternating magnetic field, typically characterized by afrequency between about 0.1 and about 2 MHz, more typically about 1.2MHz. (See FIG. 1) The magnetic field strength is typically between about3 and about 40 kA/m, although other weaker or stronger field strengthsmay be elected. The relationship between material property, frequencyand amplitude of magnetic field is terms of power dissipation isdescribed as follows: the volumetric power loss P, may be expressed asP=μ_(o)πχ″fH_(o) ², with the permeability of free space μ_(o), thesecond derivative of frequency and material dependent susceptibility χ″,frequency f, and the applied magnetic field strength H.

As shown in FIGS. 2A and 2B, chronically implantable catheters, such asones used for hydrocephalous and central venous access, typicallyexperience high failure rate due to cellular and thrombotic occlusions.Often, the failed devices need to be replaced to prevent the moreserious side effects of hydrocephalus and catheter related thrombosis.The present novel technology relates to a system 5 for reducing cloggingof catheters and like implantable devices 10. The system 5 operates bycoating or infusing catheters, cannulas and like implantable devices 10to define a layer or coating 20 containing magnetic nanoparticles 30,typically homogeneously distributed throughout, the implantable devices10 may be locally superheated through interaction of an appliedoscillating magnetic field with the magnetic nanoparticles 30sufficiently to energize and heat the device 10 to remove or reduce theformation of cellular occlusions that interfere with the properoperation of these devices 10. A cannula 10 is typically defined by anelongated tube portion 11 having an inner surface 12 and an oppositelydisposed outer surface 13. The device 10 typically has a first end 14fluidically connectable to a fluid source 16 outside the patient and asecond, oppositely disposed end 17 for fluidically communicating withthe patient.

According to one aspect of the novel technology, a self-clearingcatheter 10 includes at least one surface portion 15 coated or infused20 with magnetic nanoparticles 30. The coated or infused surfaceportions 15 are typically positioned at or near the parts of the device10 prone to occlusion by a build-up of cellular debris, such asopenings, pores, ports, bends, junctions, or the like. Once the catheter10 is implanted in a patient, the nanoparticles 30 may be energized byapplication of an oscillating magnetic field to induce localizedhyperthermia at the site of the occlusion.

According to another aspect of the novel technology, a method 100 ofremoving or reducing the formation of cellular occlusion 105 associatedwith a catheter 10 implanted in a patient includes applying no amagnetic field 120 to the catheter 10 such that magnetic nanoparticles ₃0 on a surface 15 of the catheter 10 may be energized 130 to induce 135localized hyperthermia 140 in and/or around predetermined portions 15 ofthe catheter 10. Such localized hyperthermia 140 reduces or removes 150occlusions and/or built-up masses of cellular and like debris 105.

In view of the above, it can be seen that a significant advantage ofthis system 10 is that the nanoparticles ₃o may be energized 130 toinduce localized heat (hyperthermia) 140 and thereby remove an organicocclusion 105 and/or reduce or retard the formation of the same 105,resulting in the reduction of the need for revisional surgery orreplacement of chronically implanted devices 10. The magneticnanoparticles 30 may be energized in situ and are thus activatednon-invasively.

In operation, one method 200 of removing, or reducing the formation ofcellular occlusions 105 associated with a catheter 10 implanted in apatient includes disposing 205 a plurality of magnetic nanoparticles 30on those portions or locations 15 of a catheter 10 predetermined to beat risk of clogging from accretions of cellular material 105. After thecatheter 10 is implanted 210, and it is suspected that the catheter 10has been or may be impaired by the formation or accretion of one or morecellular or organic masses 105 therein, an oscillating magnetic field215 of predetermined strength and frequency is applied 220 to thecatheter 10. The applied magnetic field 215 energizes 130 the magneticnanoparticles 30 such that they generate heat 140, and the catheter 10is heated to a high enough temperature to calcine 225 the cellularmaterial 105 sufficiently to reduce or eliminate the clogging mass 105.

The magnetic nanoparticles 30 may be infused into the catheter body 10so as to be unitary with the surface of the catheter 10 to define aninfusion layer 20, thus yielding a composite material, may be applied toan already formed catheter 10 as a coating 20, or a combination of both.The coating 20 may be mixed in any biocompatible silicone dispersions,polyurethane, polyethylene, polyimide solution or the like which isapplied, such as by dip coating, spray coating, or the like, and istypically then cured following coating. The concentration of thenanoparticles 30 typically ranges from 0.5-200 mg/ml, although lower orhigher concentrations may be chosen as desired. The coating thicknesstypically ranges from 0.1-20 microns, but may be thinner or thicker.

The magnetic nanoparticles 30 are typically disposed likely to clogportions 15 of the catheter or cannula 10, such as around an opening inthe catheter defining, when placed, a patient interface.

In some embodiments, for a catheter or cannula of a given size andcomposition, and thus with known and/or predetermined thermalproperties, the magnetic nanoparticles 30 may be distributed in or onthe cannula in a distribution pattern and/or concentration sufficient todefine a maximum temperature to which an implanted cannula 30 may beheated by an oscillating magnetic field of a given strength andfrequency, typically sufficient enough to calcine away clogs orobstructing masses, but insufficient to severely or permanently damagesurrounding tissue.

Chronically implantable devices 10 include central venous accessdevices, hydrocephalus shunt system, implantable glucose sensors,biosensors, and like devices that may suffer from functional degradationdue to biofouling be coated 20 according to the present novel technologyto yield systems 10 that can be energized to combat biofouling. Thecoating matrix is typically applied via spray or dip coating techniquesto yield a thin external membrane or layer 20 with the nanoparticles 30suspended therein. In the case of dip coating, the inner lumen of thecatheters may also be coated using low viscosity dip solution. Thenanoparticles 30 are typically mixed homogeneously to provide uniformdistribution of specific nanoparticle concentration to achievepredetermined temperature for biofouling removal, althoughnonhomogeneous distributions are contemplated to yield predeterminedtemperature gradients when energized.

It is possible to have nanoparticles or microparticles 30 infused intothe implant body (typically mad of a polymer composition), whicheliminates the need for coating process. In these variants, specificinfusion depth may be better controlled and, typically, thesuperparamagnetic particles are positioned near the surface, moretypically within 0.1 to 20 microns.

While the novel technology has been illustrated and described in detailin the drawings and foregoing description, the same is to be consideredas illustrative and not restrictive in character. It is understood thatthe embodiments have been shown and described in the foregoingspecification in satisfaction of the best mode and enablementrequirements. It is understood that one of ordinary skill in the artcould readily make a nigh-infinite number of insubstantial changes andmodifications to the above-described embodiments and that it would beimpractical to attempt to describe all such embodiment variations in thepresent specification. Accordingly, it is understood that all changesand modifications that come within the spirit of the novel technologyare desired to be protected.

I claim:
 1. A self-clearing cannula for placement in a patient,comprising: an elongated tube portion having an inner surface and anoppositely disposed outer surface, a first end fluidically connectableto a fluid source outside the patient and a second, oppositely disposedend for fluidically communicating with the patient; and a plurality ofmagnetic nanoparticles operationally connected to at least a portion ofthe cannula; wherein the metallic nanoparticles may be energized by anapplied oscillating magnetic field to heat the cannula.
 2. Theself-clearing cannula of claim 1 wherein the plurality of nanoparticlesare infused into the cannula to define a composite material.
 3. Theself-clearing cannula of claim 1 and further comprising a coating matrixbonded to the cannula, wherein the magnetic nanoparticles are suspendedin the coating matrix.
 4. The self-clearing cannula of claim 1, whereinthe magnetic nanoparticles are superparamagnetic particles.
 5. Theself-clearing cannula of claim 1 wherein the magnetic nanoparticles aredisposed at the second end.
 6. The self-cleaning cannula of claim 1wherein the magnetic nanoparticles are selected from the groupcomprising magnetite and maghemite.
 7. The self-cleaning cannula ofclaim 1 wherein the magnetic nanoparticles are sized between 10 nm andloonm in diameter.
 8. The self-cleaning cannula of claim 3 wherein thecoating matrix is between 0.1 micron and 20 microns in thickness.
 9. Amethod of removing or reducing the formation of cellular occlusionsassociated with a catheter implanted in a subject, comprising: disposinga plurality of magnetic nanoparticles on portions of a catheterpredetermined to be at risk of clogging from accretions of cellularmaterial; applying a magnetic field to the catheter; energizing themagnetic nanoparticles with the applied magnetic field to generate heat;and heating the catheter to a high enough temperature to calcine thecellular material.
 10. The method of claim 9 wherein the magneticnanoparticles are unitary with the catheter.
 11. The method of claim 9wherein the magnetic nanoparticles are coated onto the catheter.
 12. Themethod of claim 9 wherein the magnetic nanoparticles are disposed aroundan opening in the catheter defining a patient interface.
 13. The methodof claim 9 wherein the magnetic nanoparticles are present in aconcentration sufficient to define a maximum temperature to which animplanted catheter may be heated by an oscillating magnetic field of agiven strength and frequency.
 14. The method of claim 9 wherein themagnetic nanoparticles are between 10 nm and 100 nm in diameter; whereinthe magnetic nanoparticles are coated onto the catheter to define acoating between 0.1 micron thick and 20 microns thick; and wherein themagnetic nanoparticles are selected from the group comprising magnetiteand maghemite.
 15. A method of in-situ cleaning an implanted device,comprising: a) disposing a plurality of superparamagnetic nanoparticleson portions of an implantable device predetermined to be at risk ofclogging from accretions of cellular material; b) implanting the devicein a patient; c) applying an oscillating magnetic field to the device;and d) calcining organic debris clogging the device.
 16. The method ofclaim 15 wherein application of the oscillating magnetic field energizesthe superparamagnetic nanoparticles; and wherein energization of thesuperparamagnetic nanoparticles generates heat.
 17. The method of claim15 wherein the magnetic nanoparticles are coated onto the device. 18.The method of claim 17 wherein the superparamagnetic nanoparticles arebetween 10 nm and 100 nm in diameter; wherein the superparamagneticnanoparticles are coated onto the device to define a coating between 0.1micron thick and 20 microns thick; and wherein the superparamagneticnanoparticles are selected from the group comprising magnetite andmaghemite.
 19. The method of claim 17 wherein the coating varies inthickness.
 20. The method of claim 17 wherein the concentration ofsuperparamagnetic nanoparticles in the coating is non-homogeneous.